The overall objective of this research project is to develop new radiodiagnostic agents that can noninvasively detect, localize and characterize steroid hormone (estrogen and/or progesterone) responsive human mammary tumors. Such agents would be valuable in that they would assist clinicians in selecting the appropriate therapeutic regimen, in providing a prognostic indicator of long term survival, and in the sequential evaluation of the carcinoma, both primary and metastatic, in response to therapy. The role of this project is to provide a rational basis for selecting the appropriate ligand for labeling with a single photon or positron-emitting radionuclide. Factors related to estrogen and progesterone receptor affinity and selectivity have been considered as well as the radionuclides that are available in high specific activity and with desireable emission characteristics. The chemistry associated with the 11Beta-substituted-17Alpha-alkynyl progestins and estrogens, that have high receptor affinity, can be coupled with that of the bis(trialkylstannyl)arenes and ethylenes to produce intermediates that can be substituted with fluorine, bromine or iodine, all of which possess clinically useful radionuclides. From the series of haloaryl(vinyl) steroids that are synthesized, receptor binding assays and in vivo studies will indicate which compounds would possess the desireable properties for radiodiagnostic applications. The specific aims consist of: (1) The synthesis of a common intermediate from which several series of compounds can be made; (2) the site specific introduction of trial-kylstannylaryl or -vinyl groups on to the steroid nucleus; (3) the conversion to the corresponding haloaryl(vinyl) estrogens and progestins, both at millimolar scale for characterization and at the micromolar scale for potential radiolabeling; (4) the evaluation of the compounds as ligands for the estrogen and progesterone receptors in vivo; and (5) the development of structure-activity-relationships to select the most appropriate compounds for subsequent radiolabeling studies. The study emphasizes efficiency in the synthetic methodology, and in the biological evaluation, i.e., a minimal number of animals will be used to generate the structure-activity-relationships. The efficiency is also enhanced by the experience of the personnel who have extensive expertise in the designated areas of the project. As a result the entire study should be completed within the time period requested.